The escape of cyclic AMP from human diploid fibroblasts: general properties.

A variety of human diploid fibroblasts released large amounts of cAMP to the medium in a time-dependent fashion concomitant with stimulation of the cells by agonists of the adenylate cyclase. In WI-38 cells increased medium cAMP levels were detectable as quickly as increased cellular levels. Escape was not secondary to serum deprivation nor cell injury. It occurred in defined media, and was pH and temperature dependent. Elevated rates of escape were maintained for up to 24 hours after stimulation. A variety of PDE inhibitors reduced the rate of escape. A rough proportionality existed between the potencies of the compounds as potentiators of PGE1 increased cellular cAMP levels on the one hand and as inhibitors of escape on the other. In the case of IBMX, the inhibition of escape was transient, the most pronounced effect being during the first 5 minutes of incubation. In addition, a variety of compounds without significant acute effects on cellular cAMP levels inhibited escape.